Ischemic heart disease is the most common cause of morbidity and mortality in the population over the age of sixty-five. Sullivan, L. W. 1990. Healthy people 2000. N Engl J. Med. 323:1065-1067; Wei, J. Y. 1992. Age and the cardiovascular system. N Engl J. Med. 327:1735-1739; Association, A. H. 1993-1995. Heart and stroke facts statistical supplement/1994-1996. Dallas, Tex. The Association. Acute disruption of coronary blood flow causes apoptotic and necrotic death of myocardial endothelial cells and myocyte resulting in thinning of the ventricular wall, and leading to impairment of cardiac function. Cheng, W. et al. Programmed myocyte cell death affects the viable myocardium after infarction in rats. Exp Cell Res 226, 316-27 (1996). New strategies are therefore needed to prevent and reduce the pathology of cardiovascular disease associated with advancing age.
The inventors have recently demonstrated that platelet-derived growth factor (PDGF) can reduce or limit the extent of myocardial necrosis induced by ligation of the left anterior descending artery (LAD) in the rat heart. Edelberg, J. M. et al. Circulation 105, 608-13 (2002). However, PDGF treatment was most effective when administered prior to, and not at the time of, coronary occlusion. Hence, new compositions and treatment methods are needed to expand the therapeutic window of platelet-derived growth factor and to optimally protect cardiac tissues during occlusion of coronary vessels.